Brazilian Society of Hepatology and Brazilian Society of Infectious Diseases Guidelines for the Diagnosis and Treatment of Hepatitis B

Abstract Chronic hepatitis B is an important health problem that can progress to cirrhosis and complications such as hepatocellular carcinoma. There is approximately 290 million of people with chronic hepatitis B virus (HBV) infection worldwide, however only 10% of patients are currently identified.Most part of Brazil is considered of low prevalence of HBV infection but there are some regions with higher frequency of carriers. Unfortunately, many infected patients are not yet identified nor evaluated for treatment.The Brazilian Society of Infectious Diseases (SBI) and the Brazilian Society of Hepatology worked together to elaborate a guideline for diagnosis and treatment of hepatitis B. The document includes information regarding the population to be tested, diagnostic tools, indications of treatment, therapeutic schemes and also how to handle HBV infection in specific situations (pregnancy, children, immunosuppression, etc).Delta infection is also part of the guideline, since it is an important infection in some parts of the country.

Brazilian Society of Hepatology and Brazilian Society of Infectious Diseases Guidelines for the Diagnosis and Treatment of Hepatitis B.

Chronic hepatitis B is an important health problem that can progress to cirrhosis and complications such as hepatocellular carcinoma. There is approximately 290 million of people with chronic hepatitis B virus (HBV) infection worldwide, however only 10% of patients are currently identified. Most part of Brazil is considered of low prevalence of HBV infection but there are some regions with higher frequency of carriers. Unfortunately, many infected patients are not yet identified nor evaluated for treatment. The Brazilian Society of Infectious Diseases (SBI) and the Brazilian Society of Hepatology worked together to elaborate a guideline for diagnosis and treatment of hepatitis B. The document includes information regarding the population to be tested, diagnostic tools, indications of treatment, therapeutic schemes and also how to handle HBV infection in specific situations (pregnancy, children, immunosuppression, etc). Delta infection is also part of the guideline, since it is an important infection in some parts of the country.

Effectiveness of direct-acting antivirals for hepatitis C virus infection in hepatitis C/HIV coinfected individuals: A multicenter study.

In a hepatitis C virus (HCV)/HIV-positive Brazilian cohort, evaluate the safety and efficacy of HCV DAAs, the frequency of resistance substitutions in the HCV NS5A and NS5B genes and identify predictors of treatment failure.Retrospective multicenter study of HCV/HIV patients treated with sofosbuvir (SOF)-based regimens at 10 reference centers in Brazil.Clinical and virological data were collected. Genetic diversity in the NS5A and NS5B genes was assessed by direct nucleotide sequencing. The primary outcome was sustained virological response (SVR) 12 weeks after DAA completion.Of 643 HCV/HIV patients analyzed, 74.7% were male, median CD4+ T cell count was 617 cells/mm, 90% had an undetectable HIV viral load. HCV genotype 1 was detected in 80.2%, and 60% were taking at least 1 medication other than antiretroviral drugs during their DAA therapy. Cirrhosis was present in 42%. An SOF/daclatasvir (DCV) regimen was used in most patients (98%). The frequency of NS5A polymorphisms associated with clinically relevant resistance to DCV was 2%; no relevant NS5B variants were identified. The SVR12 rate was 92.8% in an intention to treat (ITT) analysis and 96% in a modified ITT (m-ITT) analysis. AE occurred in 1.6% of patients. By multivariate analysis, therapeutic failure was associated, in the m-ITT analysis, with concomitant use of anticonvulsant drugs (P = .001), age (P = .04), and female gender (P = .04).SOF/DCV regimens were associated with a high SVR rate in an HCV/HIV population. The use of concurrent anticonvulsant drugs and DAAs decreases the chances of achieving an SVR.

All-oral direct antiviral treatment for hepatitis C chronic infection in a real-life cohort: The role of cirrhosis and comorbidities in treatment response.

BACKGROUND: Hepatitis C virus (HCV) infection is the major cause of end-stage liver disease (LD) worldwide. The aim of this study was to assess sustained virological response (SVR) rates in a real-world cohort of patients with HCV infection treated with interferon-free direct antiviral agents (DAA). PATIENTS AND METHODS: All patients with genotypes 1, 2 or 3 HCV infection who started interferon-free treatment at a university hospital from December 2015 through July 2017 were included. The primary outcome was SVR at post-treatment week 12 by intention-to-treat (ITT) and modified ITT (mITT) analysis. RESULTS: Five hundred twenty seven patients were enrolled, 51.6% with cirrhosis. Most patients received sofosbuvir + daclatasvir + ribavirin (60.7%) and sofosbuvir + simeprevir (25.6%). Overall SVR rates were 90.5% for ITT and 96% for mITT. SVR rates were higher in non-cirrhotic (94.2% in ITT and 96.8% in mITT) versus cirrhotic patients (87.1% in ITT and 95.2% in mITT). In ITT and mITT assessments, SVR rates were higher in patients with Child-Pugh A (n = 222, 88.7% and 95.7%, respectively) versus Child-Pugh B or C (n = 40, 80% and 90%, respectively); SVR rates were higher in patients with genotype 1 (n = 405, 92.1% and 98.2%), followed by genotype 2 (n = 13, 84.6% and 92.7%) and genotype 3 (n = 109, 84.4% and 88.4%). Lower comorbidity index (p = 0.0014) and absence of cirrhosis (p = 0.0071) were associated with SVR. Among cirrhotic patients, lower Model for End-Stage Liver Disease (p = 0.0258), higher albumin (p = 0.0015), and higher glomerular filtration rate (p = 0.0366) were related to SVR. Twenty-two cirrhotic patients (8%) had clinical liver decompensation during treatment. Complications of advanced LD were responsible for discontinuation of treatment and death in 12 and 7 patients, respectively. CONCLUSION: Treatment with all-oral DAA achieved high SVR rates, particularly in patients without cirrhosis and few comorbidities. Advanced LD is associated to poor outcome, such as treatment failure and death.

Controlled attenuation parameter for steatosis grading in chronic hepatitis C compared with digital morphometric analysis of liver biopsy: impact of individual elastography measurement quality.

BACKGROUND AND OBJECTIVE: Controlled attenuation parameter (CAP) diagnostic performance for steatosis grading has been controversial and considerable observer-related variability in liver biopsy has been reported. This is a subanalysis of a larger chronic hepatitis C study on noninvasive fibrosis staging. MATERIALS AND METHODS: Patients were prospectively enrolled for paired liver biopsy and transient elastography. Biopsy fragments were subjected to digital morphometric steatosis quantification. Associated patient and technical factors, including a newly described elastogram quality score, were evaluated. RESULTS: A total of 312 patients were included in the final analysis. The mean liver stiffness was 8.7±2.1 kPa. Morphometry showed S0 in 19.2% of patients, S1 in 28.5%, S2 in 31.1%, and S3 in 21.2%. CAP showed S0 in 11.2% of patients, S1 in 26.6%, S2 in 56.7%, and S3 in 5.4%. Spearman coefficient showed a positive and independent correlation between CAP and morphometric analysis (r=0.48, P<0.05), except for distinguishing S1 and S2 (P=0.11). Area under the receiver operating characteristic curves for the presence or absence of steatosis was 0.944; differentiation between levels I, II, and III were 0.776, 0.812, and 0.879. Elastogram quality independently predicted accuracy [odds ratio (OR): 6.95, 95% confidence interval (95%CI): 4.45-9.06 as well as CAP interquartile range OR: 2.81, 95%CI: 1.67-3.99] and liver stiffness (OR: 0.78, 95%CI: 0.51-0.80). CONCLUSION: We present an external validation for CAP against the objective steatosis quantification provided by digital morphometry. Fairly good performance indicators were found, except for S1 versus S2 differentiation. Variability and higher liver stiffness were associated with lower performance. Achieving higher quality measurements, however, overcame such limitations with excellent accuracy.

Diagnosis and staging of fibrosis in patients with chronic hepatitis C: comparison and critical overview of current strategies.

In the past years, what has always been considered undisputed true in liver fibrosis staging has been challenged. Diagnostic performance of histological evaluation has proven to be significantly influenced by sample- and observer-related variabilities. Differentiation between lower levels of fibrosis remains difficult for many, if not all, test modalities, including liver biopsy but, perhaps, such a distinction is not indispensable in light of current therapeutic approaches. Biomarkers and elastography offer, nonetheless, high predictive values for advanced fibrosis and cirrhosis and correlate well with liver-related outcomes. Necroinflammation, steatosis, and hemodynamic changes may significantly interfere with elastography-based techniques, and longitudinal follow-up strategies must be tailored in light of these findings. Knowledge of different test modalities and diagnostic performance indicators can allow for better clinical decision-making and resource allocation.

Predictors of early discontinuation of interferon-free direct antiviral agents in patients with hepatitis C virus and advanced liver fibrosis: results of a real-life cohort.

AIM: The aim of this study was to determine risk factors for premature treatment discontinuation among patients with hepatitis C and advanced fibrosis with advanced fibrosis treated with interferon (IFN)-free direct antiviral agents (DAA)-based therapy. PATIENTS AND METHODS: We included all patients with chronic hepatitis C virus infection and advanced liver fibrosis in whom treatment was initiated with IFN-free DAA therapy at a university hospital from December 2015 through June 2016. We prospectively collected data from medical records using standardized questionnaires and evaluated them using Epi Info 7.1.2.0. The primary outcome was treatment interruption and associated factors. RESULTS: In total, 214 patients were included in this study; 180 patients were treated with sofosbuvir (SOF)+daclatasvir±ribavirin (RBV), 31 received SOF+simeprevir±RBV, and three were treated with SOF+RBV. Treatment discontinuation rate was 8.9% (19 patients) and cirrhotic decompensation was the main reason [8 (42.1%)]. Among patients with Child B or C cirrhosis (31), 10 (32.2%) prematurely interrupted treatment. The risk factors for treatment discontinuation in univariate analysis were older age (P=0.0252), higher comorbidity index (P=0.0078), higher model for end-stage liver disease (P<0.0001), higher fibrosis index based on the 4 factores (P=0.0122), and lower hemoglobin (P=0.0185) at baseline. Multivariate analysis showed that older age (odds ratio: 1.1, 95% confidence interval: 1.02-1.19) and higher model for end-stage liver disease (odds ratio: 1.27, 95% confidence interval: 1.03-1.56) were associated with premature treatment interruption. CONCLUSION: Older age and advanced liver disease were related to treatment interruption. Identification of risk factors associated with treatment discontinuation is important to recognize patients who should be followed up closely during treatment, ando those whom possibly may not benefit from immediate DAA treatment or should be followed up closely during treatment.

Hepatitis C virus: Promising discoveries and new treatments.

Despite advances in therapy, hepatitis C virus (HCV) infection remains an important global health issue. It is estimated that a significant part of the world population is chronically infected with the virus, and many of those affected may develop cirrhosis or liver cancer. The virus shows considerable variability, a characteristic that directly interferes with disease treatment. The response to treatment varies according to HCV genotype and subtype. The continuous generation of variants (quasispecies) allows the virus to escape control by antivirals. Historically, the combination of ribavirin and interferon therapy has represented the only treatment option for the disease. Currently, several new treatment options are emerging and are available to a large part of the affected population. In addition, the search for new substances with antiviral activity against HCV continues, promising future improvements in treatment. Researchers should consider the mutation capacity of the virus and the other variables that affect treatment success.

Chronic hepatitis C virus infection: it is not only about the liver.

BACKGROUND AND AIMS: Although hepatitis B virus (HBV) and hepatitis C virus (HCV) are both hepatotropic and quite similar in terms of clinical manifestations and histopathology, their respective infections are distinct in terms of epidemiology and prognosis. Recognizing the differences between patients with HBV and HCV infection with respect to demographic characteristics, prevalence of comorbidities, and presence of lifestyle factors aids the proper treatment of these patients. We aimed to compare two populations with chronic viral liver disease (chronic HCV and chronic HBV), each of them with resolved hepatitis C. PATIENTS AND METHODS: We included patients referred to a municipal reference clinic from March 2009 through May 2012. Patient data were collected using standardized questionnaires at the patients' first visit to clinic. Questionnaires included epidemiological information, presence of comorbidities, and lifestyle. RESULTS: A total of 756 patients were included in the study, 348 (46.0%) with chronic HCV infection, 176 (23.3%) with chronic HBV infection, and 232 (30.7%) with resolved HCV infection. Multivariate analysis including patients with chronic HCV infection and chronic HBV infection indicated that age [adjusted odds ratio (AOR)=1.06; 95% confidence interval (CI): 1.03-1.08], alcohol abuse (AOR=1.58; 95% CI: 1.01-2.49), smoking (AOR=1.64; 95% CI: 1.00-2.17), and illicit drug (AOR=2.92; 95% CI: 1.69-5.02) use were associated independently with chronic HCV infection. Multivariate analyses including patients with chronic HCV infection and those patients with resolved HCV infection, presence of at least one comorbidity (AOR=1.94; 95% CI: 1.12-3.3), illicit drug use (AOR=3.24; 95% CI: 1.90-5.54), and age (AOR=1.03; 95% CI: 1.01-1.05) were independently associated with chronic HCV infection. Age (AOR=0.98; 95% CI: 0.96-0.99) and male sex (AOR=1.93; 95% CI: 1.26-2.95) were the only variables associated significantly with chronic HBV infection in the multivariate analysis between patients with chronic HBV infection and resolved HCV infection. CONCLUSION: Our results highlight that patients with chronic HCV infection are complex and require a multidisciplinary approach during patient follow-up and clinical management.

Hepatites Virais: passado, presente e futuro / Viral Hepatitis: past, present and future

A disseminação das hepatites virais é consequência de amplas e marcantes mudanças que ocorreram nas últimas três décadas do século XX, especialmente na sociedade ocidental. A emergência das hepatites virais resultou em significativa redução da qualidade de vida e sobrevida entre aqueles que contraíram a infecção. O impac¬to das hepatites virais varia de acordo com os diferentes níveis de desenvolvimento socioeconômico das populações e de fatores emer¬gentes na sua transmissão. Por fim, importantes avanços científicos e sociais foram otbtidos, mas ainda insuficientes para o controle dessas infecções. A epidemiologia das hepatites virais no Século XXI reflete tanto o impacto positivo de medidas de prevenção como o impacto negativo de padrões de transmissão históricos e emergen¬tes. As hepatites virais são doenças de dois mundos: um, no qual as novas infecções restringem-se a padrões emergentes de transmissão e o tratamento é acessível; outro, no qual tanto padrões históricos como emergentes de transmissão possibilitam novas infecções e o tratamento é pouco acessível

The spread of viral hepatitis is the result of extensive and remarkable social changes that occurred in the last three decades of the twentieth century, especially in Western society. The emergence of viral hepatitis resulted in a significant reduction in quality of life and survival among those who contracted the infection. The impact of viral hepatitis varies with the different levels of socioeconomic development of populations and emerging factors in its transmission. Finally, important scientific and social advances have been achieved, but still insufficient to control these infections. The epidemiology of viral hepatitis in the XXI century reflects both the positive impact of preventive measures and the negative impact of historical and transmission emerging patterns. Viral hepatitis is a disease of two worlds, one where new infections are restricted to emerging patterns of transmission and treatment is available, another where both historical patterns and emerging new infections allow transmission and access to treatment is restricted

Hepatitis B virus surface antigen seroconversion in HIV-infected individual after pegylated interferon-alpha treatment: a case report.

Hepatitis B virus (HBV) infects from 6 to 14% of HIV-infected individuals. Concurrent HIV/HBV infection occurs due to the overlapping routes of transmission, particularly sexual and parenteral. HIV-infected patients that have acute hepatitis B have six times greater risk of developing chronic hepatitis B, with higher viral replication, rapid progression to end-stage liver disease and shorter survival. The coinfection is also associated with poor response to hepatitis B treatment with interferon-alpha and increased liver toxicity to the antiretroviral therapy. Herein, we describe the case of a 35-year-old man who engages in sex with men and presented with newly diagnosed HIV-1, serological markers for acute hepatitis B and progression to chronic hepatitis B infection (HBsAg+ > 6 months, high alanine aminotransferase levels and moderate hepatitis as indicated by liver biopsy). Lacking indication of antiretroviral treatment (CD4 768 cells/mm3), he was treated with pegylated-interferon alpha2b (1.5 mg/kg/week) by subcutaneous injection for 48 weeks. Twelve weeks after treatment, the patient presented HBeAg seroconversion to anti-HBe. At the end of 48 weeks, he presented HBsAg seroconversion to anti-HBs. One year after treatment, the patient maintained sustained virological response (undetectable HBV-DNA). The initiation of antiretroviral therapy with nucleosides and nucleotides is recommended earlier for coinfected individuals. However, this report emphasizes that pegylated interferon remains an important therapeutic strategy to be considered for selected patients, in whom the initiation of HAART may be delayed.

Hepatitis B virus surface antigen seroconversion in HIV-infected individual after pegylated interferon-alpha treatment: a case report

Hepatitis B virus (HBV) infects from 6 to 14% of HIV-infected individuals. Concurrent HIV/HBV infection occurs due to the overlapping routes of transmission, particularly sexual and parenteral. HIV-infected patients that have acute hepatitis B have six times greater risk of developing chronic hepatitis B, with higher viral replication, rapid progression to end-stage liver disease and shorter survival. The coinfection is also associated with poor response to hepatitis B treatment with interferon-alpha and increased liver toxicity to the antiretroviral therapy. Herein, we describe the case of a 35-year-old man who engages in sex with men and presented with newly diagnosed HIV-1, serological markers for acute hepatitis B and progression to chronic hepatitis B infection (HBsAg+ > 6 months, high alanine aminotransferase levels and moderate hepatitis as indicated by liver biopsy). Lacking indication of antiretroviral treatment (CD4 768 cells/mm 3 ), he was treated with pegylated-interferon alpha2b (1.5 mg/kg/week) by subcutaneous injection for 48 weeks. Twelve weeks after treatment, the patient presented HBeAg seroconversion to anti-HBe. At the end of 48 weeks, he presented HBsAg seroconversion to anti-HBs. One year after treatment, the patient maintained sustained virological response (undetectable HBV-DNA). The initiation of antiretroviral therapy with nucleosides and nucleotides is recommended earlier for coinfected individuals. However, this report emphasizes that pegylated interferon remains an important therapeutic strategy to be considered for selected patients, in whom the initiation of HAART may be delayed.(AU)

Hepatitis B virus surface antigen seroconversion in HIV-infected individual after pegylated interferon-alpha treatment: a case report

Hepatitis B virus (HBV) infects from 6 to 14% of HIV-infected individuals. Concurrent HIV/HBV infection occurs due to the overlapping routes of transmission, particularly sexual and parenteral. HIV-infected patients that have acute hepatitis B have six times greater risk of developing chronic hepatitis B, with higher viral replication, rapid progression to end-stage liver disease and shorter survival. The coinfection is also associated with poor response to hepatitis B treatment with interferon-alpha and increased liver toxicity to the antiretroviral therapy. Herein, we describe the case of a 35-year-old man who engages in sex with men and presented with newly diagnosed HIV-1, serological markers for acute hepatitis B and progression to chronic hepatitis B infection (HBsAg+ > 6 months, high alanine aminotransferase levels and moderate hepatitis as indicated by liver biopsy). Lacking indication of antiretroviral treatment (CD4 768 cells/mm 3 ), he was treated with pegylated-interferon alpha2b (1.5 mg/kg/week) by subcutaneous injection for 48 weeks. Twelve weeks after treatment, the patient presented HBeAg seroconversion to anti-HBe. At the end of 48 weeks, he presented HBsAg seroconversion to anti-HBs. One year after treatment, the patient maintained sustained virological response (undetectable HBV-DNA). The initiation of antiretroviral therapy with nucleosides and nucleotides is recommended earlier for coinfected individuals. However, this report emphasizes that pegylated interferon remains an important therapeutic strategy to be considered for selected patients, in whom the initiation of HAART may be delayed.

Hepatitis C infection and chronic renal diseases.

Hepatitis C virus (HCV) infection and chronic renal diseases can be linked in two different ways. Some forms of renal disease are precipitated by HCV infection, while patients with end-stage renal disease are at increased risk for acquiring HCV infection. Patients with chronic HCV infection and renal disease have a poor prognosis. Most studies on treatment of HCV and renal diseases have been uncontrolled trials with small number of subjects. So, there is a lack of evidence-based recommendations and guidelines on the management of this condition. In this review, we will attempt to provide the most recent insights on HCV infection both as a extrahepatic manifestations and as a complication of end-stage renal patients.

Therapeutic effectiveness of biosimilar standard interferon versus pegylated interferon for chronic hepatitis C genotypes 2 or 3.

BACKGROUND: Pegylated interferon (Peg-IFN) and standard interferon (IFN) play a significant role in the treatment of hepatitis C virus (HCV) infection. Biosimilar standard IFN is widely available in Brazil for the treatment of HCV infection genotypes 2 or 3, but its efficacy compared to Peg-IFN is unknown. OBJECTIVE: To compare the sustained virological response (SVR) rates following treatment with biosimilar standard IFN plus ribavirin (RBV) versus Peg-IFN plus RBV in patients with HCV genotypes 2 or 3 infection. METHODS: A retrospective cohort study was conducted in patients with HCV genotypes 2 or 3 infection treated with biosimilar standard IFN plus RBV or with Peg-IFN plus RBV. SVR rates of the two treatments were compared. RESULTS: From January 2005 to December 2010, 172 patients with a mean age of 44 +/- 9.3 years were included. There were eight (4.7%) patients with HCV genotype 2 infections. One hundred fourteen (66.3%) were treated with biosimilar standard IFN plus RBV, whist 58 (33.7%) patients were treated with Peg-IFN plus RBV. Between the two groups, there were no significant differences regarding age, gender, glucose level, platelet count, hepatic necroinflammatory grade, and hepatic fibrosis stage. Overall, 59.3% (102/172) patients had SVR. In patients treated with Peg-IFN plus RBV, 79.3% (46/58) had SVR compared to 49.1% (56/114) among those treated with biosimilar standard IFN plus RBV (p = 0.0001). CONCLUSION: In patients with HCV genotypes 2 or 3 infection, a higher SVR was observed in patients receiving Peg-IFN plus RBV related to patients treated with biosimilar standard IFN plus RBV.

Therapeutic effectiveness of biosimilar standard interferon versus pegylated interferon for chronic hepatitis C genotypes 2 or 3

BACKGROUND: Pegylated interferon (Peg-IFN) and standard interferon (IFN) play a significant role in the treatment of hepatitis C virus (HCV) infection. Biosimilar standard IFN is widely available in Brazil for the treatment of HCV infection genotypes 2 or 3, but its efficacy compared to Peg-IFN is unknown. OBJECTIVE: To compare the sustained virological response (SVR) rates following treatment with biosimilar standard IFN plus ribavirin (RBV) versus Peg-IFN plus RBV in patients with HCV genotypes 2 or 3 infection. METHODS: A retrospective cohort study was conducted in patients with HCV genotypes 2 or 3 infection treated with biosimilar standard IFN plus RBV or with Peg-IFN plus RBV. SVR rates of the two treatments were compared. RESULTS: From January 2005 to December 2010, 172 patients with a mean age of 44 +/- 9.3 years were included. There were eight (4.7%) patients with HCV genotype 2 infections. One hundred fourteen (66.3%) were treated with biosimilar standard IFN plus RBV, whist 58 (33.7%) patients were treated with Peg-IFN plus RBV. Between the two groups, there were no significant differences regarding age, gender, glucose level, platelet count, hepatic necroinflammatory grade, and hepatic fibrosis stage. Overall, 59.3% (102/172) patients had SVR. In patients treated with Peg-IFN plus RBV, 79.3% (46/58) had SVR compared to 49.1% (56/114) among those treated with biosimilar standard IFN plus RBV (p = 0.0001). CONCLUSION: In patients with HCV genotypes 2 or 3 infection, a higher SVR was observed in patients receiving Peg-IFN plus RBV related to patients treated with biosimilar standard IFN plus RBV.

Retreatment of hepatitis C patients with pegylated interferon combined with ribavirin in non-responders to interferon plus ribavirin. Is it different in real life?

BACKGROUND: More than 50% of hepatitis C viruses (HCV)-infected patients do not respond to the classical Interferon (IFN)/Ribavirin (RBV) combination therapy. The aim of this study was to evaluate the efficacy of retreatment with Peg-Interferon alpha-2b (PEG-IFN alpha-2b) plus RBV, in patients with HCV, genotypes 1 or 3, who were non-responders to the previous standard treatment with IFN/RBV. METHODS: In the period 2005-2007, a total of 238 HCV chronic patients were non-responders to previous treatment with IFN plus RBV. Of these 130 agreed to be retreated with PEG-IFN alpha-2b and participated in this evaluation (90 with genotype 1 HCV and 40 with genotype 3 HCV). Patients were retreated at assisted IFN application hubs in compliance with the country's public health system rules. They received subcutaneous PEG-IFN alpha-2b, 1.5 microg, once weekly, associated with RBV, through the oral route, with doses determined according to weight (1,000 mg if weight 75 kg). Patients with genotype 1 HCV were retreated for over 48 weeks and patients with genotype 3 HCV for over 24 weeks. HCV-RNA was tested by polymerase chain reaction (PCR) at baseline, at week 12, at the end of the treatment, and 6 months thereafter. The predictiveness of week 12 in the development of a sustained virologic response (SVR) was also evaluated. Patients with negative HCV-RNA at week 12 were considered as early virologic responders (EVR). RESULTS: EVR was observed in 25% of the patients with genotype 1 HCV and in 64% of the patients genotype 3 HCV (risk = 2.075 and p-value = 0.0414). SVR was observed in 22.2% of the patients with genotype 1 HCV and in 40% with genotype 3 HCV (intention-to-treat analysis). The positive predictive value (PPV) of the HCV-RNA testing at week 12, in order to obtain the SVR, was 65% for genotype 1 and 56% for genotype 3, and the negative predictive value (NPV) was 88% for genotype 1 and 89% for genotype 3. CONCLUSIONS: PEG-IFN alpha-2b plus weight-based ribavirin is effective in re-treating previous interferon-alpha plus RBV failure; 22.2% of the patients with genotype 1 HCV and 40% of patients with genotype 3 HCV achieved SVR.

Extended treatment with interferon and ribavirin in a hemodialysis patient with chronic hepatitis C.

Hemodialysis patient with chronic HCV infection,who was started on monotherapy with interferon.Qualitative HCV RNA remained positive at 12 weeks of treatment; ribavirin was associated. HCV RNA was negative at week 24 and treatment was extended to 72 weeks. HCV RNA negative six months after treatment.

Extended treatment with interferon and ribavirin in a hemodialysis patient with chronic hepatitis C

Hemodialysis patient with chronic HCV infection,who was started on monotherapy with interferon.Qualitative HCV RNA remained positive at 12 weeks of treatment; ribavirin was associated. HCV RNA was negative at week 24 and treatment was extended to 72 weeks. HCV RNA negative six months after treatment.

Hepatitis B virus: molecular genotypes and HBeAg serological status among HBV-infected patients in the southeast of Brazil.

BACKGROUND: Knowledge of HBV genotype is very important for clinical treatment. Studies have suggested possible pathogenic and therapeutic differences among HBV genotypes. The aim of this study was to determine HBV subtypes and genotypes in HBV-infected patients in our region (southeast Brazil) and to correlate results with clinical and histopathological data. METHODS: One hundred and thirty-nine HBsAg-positive patients were included in the study. All patients were anti-HCV and anti-HIV negative (64% male; mean age 42 +/- 14.5 years; range 7-80 years; 84% Caucasian) and were followed up at the University Hospital. A method for genotyping and subtyping HBV by partial HBsAg gene sequencing with primers common to all known genotypes was used. The viral load was measured by Amplicor Monitor assay (Roche). RESULTS: HBV genotype A was the most prevalent (55%), while genotypes C, D and F were found in 3%, 38% and 4% of HBV-infected patients, respectively. Among the patients infected by genotype A, 18.3% (14/76) were African descendents and, among the patients infected by genotype D, 11.3% (6/53) were also African descendents. In the four patients infected with genotype C, 2 were Asian descendents and 2 were Caucasians. All (7) genotype F infected patients were Caucasians. Seventy percent of our HBsAg-positive patients were HBeAg negative (62% genotypes A; 26.2% D; 7.1% C and 4.7%F). The viral load of HBV-DNA was about 5 times higher in HBeAg-positive than in HBeAg-negative patients. About 40% of these patients had alanine aminotransferase of up to 1.5 times the normal level. The mean stage of fibrosis in genotype A patients (2.8) was significantly higher than the mean stage of fibrosis in genotype D patients (2.0) (P = 0.0179). CONCLUSION: The genotypes encountered in our HBV-infected patients were apparently a consequence of the types of immigration that occurred in our region, where European and African descendents predominate. The HBeAg-negative status predominated, possibly due to the length of time of infection. The viral load in HBeAg-positive patients was higher than in HBeAg-negative individuals. The fibrosis grade in genotype A-infected patients was more advanced than genotype D-infected patients.